2-Decarboxy-2-hydroxymethyl-ω-phenyl-PGA or 9-deoxy-9,10-didehydro-PGD analogs

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl is replaced by a primary alcohol. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 647,357, filed Jan. 8, 1976, now issued as U.S. Pat. No. 4,055,602.

The present invention relates to prostaglandin analogs, for which the essential material constituting disclosure therefor is incorporated by reference here from U.S. pat. No. 4,055,602, issued Oct. 25, 1977. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein Y is trans--CH═CH--; wherein M₁ is ##STR2## wherein R₅ is hydrogen or methyl; WHEREIN L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is methyl only when the other is hydrogen or methyl;Wherein Z₂ is

    cis-CH═CH--CH.sub.2 --(CH.sub.2).sub.g --CF.sub.2 --;

    cis-CH.sub.2 --CH═CH--(CH.sub.2).sub.g --CH.sub.2 --; or

    --(CH.sub.2).sub.3 --(CH.sub.2).sub.g --CF.sub.2 --;

wherein g is one, 2, or 3; and Wherein s is zero, one, 2, or 3 and T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl.
 2. A compound according to claim 1, wherein ##STR5##
 3. A compound according to claim 2, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 4. A compound according to claim 3, wherein Z₂ is cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 5. A compound according to claim 4, wherein g is one.
 6. A compound according to claim 5, wherein at least one of R₃ and R₄ is fluoro.
 7. A compound according to claim 6, wherein R₃ and R₄ are both fluoro.
 8. A comound according to claim 7, wherein R₅ is methyl.
 9. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-15methyl-17-phenyl-18,19,20-trinor-PGA₂, a compound according to claim
 8. 10. A compound according to claim 7, wherein R₅ is hydrogen.
 11. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-17-phenyl-18,19,20-trinor-PGA₂, a compound according to claim
 10. 12. A compound according to claim 5, wherein at least one of R₃ and R₄ is methyl.
 13. A compound according to claim 12, wherein R₃ and R₄ are both methyl.
 14. A compound according to claim 13, wherein R₅ is methyl.
 15. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-PGA₂, a compound according to claim
 14. 16. A compound according to claim 15, wherein R₅ is hydrogen.
 17. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGA₂, a compound according to claim
 16. 18. A compound according to claim 5, wherein R₃ and R₄ are both hydrogen.
 19. A compound according to claim 18, wherein R₅ is hydrogen.
 20. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-17-phenyl-18,19,20-trinor-PGA₂, a compound according to claim
 19. 21. A compound according to claim 18, wherein R₅ is hydrogen.
 22. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-17-phenyl-18,19,20-trinor-PGA₂, a compound according to claim
 21. 23. A compound according to claim 3, wherein Z₂ is --(CH₂)₃ --(CH₂)_(g) --CF₂ --.
 24. A compound according to claim 23, wherein g is one.
 25. A compound according to claim 24, wherein at least one of R₃ and R₄ is fluoro.
 26. A compound according to claim 25, wherein R₃ and R₄ are both fluoro.
 27. A compound according to claim 26, wherein R₅ is methyl.
 28. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-15-methyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 27. 29. A compound according to claim 26, wherein R₅ is hydrogen.
 30. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 29. 31. A compound according to claim 24, wherein at least one of R₃ and R₄ is methyl.
 32. A compound according to claim 31, wherein R₃ and R₄ are both methyl.
 33. A compound according to claim 32, wherein R₅ is methyl.
 34. 2-Decarboxy-2-hydroxymetyl-2,2-difluoro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 33. 35. A compound according to claim 32, wherein R₅ is hydrogen.
 36. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 35. 37. A comound according to claim 24, wherein Rhd 3 and R₄ are both hydrogen.
 38. A compound according to claim 37, wherein R₅ is methyl.
 39. 2-Decaroboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 38. 40. A compound according to claim 37, wherein R₅ is hydrogen.
 41. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 40. 42. A compound according to claim 3, wherein Z₂ is cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 43. A compound according to claim 42, wherein g is one.
 44. A compound according to claim 43, wherein at least one of R₃ and R₄ is fluoro.
 45. A compound according to claim 44, wherein R₃ and R₄ are both fluoro.
 46. A compound according to claim 45, wherein R₅ is methyl.
 47. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15-methyl-16,16-difluoro-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 46. 48. A compound according to claim 45, wherein R₅ is hydrogen.
 49. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16,16-difluoro-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 48. 50. A compound according to claim 43, wherein at least one of R₃ and R₄ is methyl.
 51. A compound according to claim 50, wherein R₃ and R₄ are both methyl.
 52. A compound according to claim 51, wherein R₅ is methyl.
 53. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 52. 54. A compound according to claim 51, wherein R₅ is hydrogen.
 55. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 54. 56. A compound according to claim 43, wherein R₃ and R₄ are both hydrogen.
 57. A compound according to claim 56, wherein R₅ is methyl.
 58. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15-methyl-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 57. 59. A compound according to claim 56, wherein R₅ is hydrogen.
 60. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-17-phenyl-18,19,20-trinor-PGA₁, a compound according to claim
 59. 61. A compound according to claim 1, wherein ##STR6##
 62. A compound according to claim 61, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 63. A compound according to claim 62, wherein Z₂ is cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --.
 64. A compound according to claim 63, wherein g is one.
 65. A compound according to claim 64, wherein at least one of R₃ and R₄ is fluoro.
 66. A compound according to claim 65, wherein R₃ and R₄ are both fluoro.
 67. A compound according to claim 66, wherein R₅ is methyl.
 68. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-15-methyl-b 17-phenyl-18,19,20-trinor-9-deoxy-9,10,-didehydro-PGD₂, a compound according to claim
 67. 69. A compound according to claim 66, wherein R₅ is hydrogen.
 70. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-17-phenyl-18,19,20-9-deoxy-9,10-didehydro-PGD₂, a compound according to claim
 69. 71. A compound according to claim 64, wherein at least one of R₃ and R₄ is methyl.
 72. A compound according to claim 71, wherein R₃ and R₄ are both methyl.
 73. A compound according to claim 72, wherein R₅ is methyl.
 74. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₂, a compound according to claim
 73. 75. A compound according to claim 72, wherein R₅ is hydrogen.
 76. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16,16-dimethyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₂, a compound according to claim
 75. 77. A compound according to claim 64, wherein R₃ and R₄ are both hydrogen.
 78. A compound according to claim 77, wherein R₅ is hydrogen.
 79. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₂, a compound according to claim
 78. 80. A compound according to claim 77, wherein R₅ is hydrogen.
 81. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₂, a compound according to claim
 80. 82. A compound according to claim 62, wherein Z₂ is --(CH₂)₃ --(CH₂)_(g) --CF₂ --.
 83. A compound according to claim 82, wherein g is one.
 84. A compound according to claim 83, wherein at least one of R₃ and R₄ is fluoro.
 85. A compound according to claim 84, wherein R₃ and R₄ are both fluoro.
 86. A compound according to claim 85, wherein R₅ is methyl.
 87. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-15methyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 86. 88. A compound according to claim 85, wherein R₅ is hydrogen.
 89. 2-Decarboxy-2-hydroxymethyl-2,2,16,16-tetrafluoro-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 88. 90. A compound according to claim 83, wherein at least one of R₃ and R₄ is methyl.
 91. A compound according to claim 90, wherein R₃ and R₄ are both methyl.
 92. A compound according to claim 91, wherein R₅ is methyl.
 93. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 92. 94. A compound according to claim 91, wherein R₅ is hydrogen.
 95. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-16,16-dimethyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 94. 96. A compound according to claim 83, wherein R₃ and R₄ are both hydrogen.
 97. A compound according to claim 96, wherein R₅ is methyl.
 98. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-15-methyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 97. 99. A compound according to claim 96, wherein R₅ is hydrogen.
 100. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 99. 101. A compound according to claim 62, wherein Z₂ is cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 102. A compound according to claim 101, wherein g is one.
 103. A compound according to claim 102, wherein at least one of R₃ and R₄ is fluoro.
 104. A compound according to claim 103, wherein R₃ and R₄ are both fluoro.
 105. A compound according to claim 104, wherein R₅ is methyl.
 106. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15-methyl-16,16-difluoro-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 105. 107. A compound according to claim 104, wherein R₅ is hydrogen.
 108. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16,16-difluoro-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 107. 109. A compound according to claim 102, wherein at least one of R₃ and R₄ is methyl.
 110. A compond according to claim 109, wherein R₃ and R₄ are both methyl.
 111. A compound according to claim 110, wherein R₅ is methyl.
 112. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 111. 113. A compound according to claim 110, wherein R₅ is hydrogen.
 114. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 113. 115. A compound according to claim 102, wherein R₃ and R₄ are both hydrogen.
 116. A compound according to claim 115, wherein R₅ is methyl.
 117. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-15-methyl-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 116. 118. A compound according to claim 115, wherein R₅ is hydrogen.
 119. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-17-phenyl-18,19,20-trinor-9-deoxy-9,10-didehydro-PGD₁, a compound according to claim
 118. 